The present invention relates to vehicles for delivering an active ingredient, and more particularly, to vehicles which release the active ingredient over a prolonged period of time.
Controlled release of an active ingredient over time has significant advantages in numerous applications over one or more bolus releases of the active ingredient. Sustained release over an extended period of time enables application of a lower overall dose of the active ingredient while minimizing wide concentration gradients which result from multiple bolus applications. For example, in the case of a cream having dermatologic activity, a greater than necessary concentration of the active ingredient must often be applied due to various factors such as dilution due to perspiration, UV-initiated degradation, or volatilization which reduce its efficacy. Thus, the concentration of the active ingredient may start out much higher than necessary, implicating toxic dose or allergy considerations, then decline through and below the effective dosage range. Flattening the dosage curve and extending the delivery time thereof through the use of time release vehicles can achieve significant advantages in many fields, including medicine, cosmetics, pesticides, herbicides, fertilizers and others.
Known time release vehicles generally fall into one of several categories. A first type of carrier comprises beads or droplets of active ingredient encapsulated in a polymeric coating designed to solubilize or rupture under predetermined circumstances to release the active ingredient. This first type of microencapsulation generally provides a bolus release of the active ingredient upon the occurrence of the predetermined event to rupture the membrane. For example, U.S. Pat. No. 3,786,123 to Katzen discloses encapsulation of nutrients in a high protein content vegetable composition which solubilizes in the environment of the digestive tract. ,
Another known microencapsulation technique, which achieves a more prolonged release of active ingredient over time, utilizes a microencapsulation coating or membrane which is either semi-permeable or porous to allow the active ingredient to diffuse out of the microcapsule.
A third type of vehicle comprises a porous matrix having an active ingredient dissolved or dispersed throughout. The delivery rate of the active ingredient is a function of the porosity of the structure, the solubility of the active ingredient, and other driving forces such as diffusivity responsible for liberating the active ingredient from the matrix. For example, U.S. Pat. No. 4,690,825 to Won discloses a time release delivery vehicle comprising a spherical polymeric bead having a network of pores with an active ingredient held within the network to provide controlled release of the active ingredient.
For some applications, however, the synthetic polymer bead carriers are disadvantageous. Microencapsulation in a polymeric bead or shell is typically achieved by adding the active ingredient to a monomer solution prior to or during the polymerization step. As the porous polymer structure is formed, active ingredient is entrapped within the pores. It is also possible that excess monomer can be trapped within the pores to be released with the active ingredient. The presence of monomer presents a potential health hazard. Synthetic polymer microencapsulation vehicles typically have the further disadvantage of imparting an undesirable gritty feel to topical creams made up for cosmetic and dermatologic applications. Regardless of the application, synthetic polymers used for microencapsulation are generally not biodegradable. Therefore, these polymers may not be used in powder forms if there is a possibility of inhalation. A small nondegradable particle, if inhaled, can present the possibility of serious health consequences if it remains in the body. In addition, some synthetic polymers can decompose to give off hazardous chemicals under certain circumstances. These problems limit the usefulness or detract from the desirability of synthetic polymers in a number of applications.